Rationale, Scientific Objective, and Aims: The NuCress™ scaffold technology is a transformative medical device designed to promote fast, functional bone regeneration in patients suffering catastrophic injuries. When approved by the Food and Drug Administration (FDA), this tool will give surgeons a highly versatile option to treat the most challenging and devastating bone injuries. Developed in part with support from the Department of Defense, the NuCress™ scaffold offers speed, versatility, and results far superior to the current standards of practice for bone regeneration. The scaffold’s performance in regenerating bone has been proven, and we now seek funding to move it through the final phases of preparation for an application for FDA 510(k) medical device status. In this application, we seek to develop the next generation of the scaffold and expand the NuCress™ scaffold’s market and clinical portfolio by tuning the scaffold formulation specifically for antibiotic drug loading and elution to simultaneously and rapidly fight infection and regenerate bone. This new technology is designed for extremely complex and contaminated bone defects with a high risk of infections and was developed for use in far forward surgical theaters in a prolonged field care (PFC) environment, given its ability to release large amounts of antibiotics to prevent biofilm formation and facilitate bone formation. The ability of the scaffold to deliver antibiotics is critical for both military and civilian patients, as complex bone breaks frequently involve debilitating infections that complicate healing and prolong recovery.

In this application, we will adapt the formulation of the scaffold for optimal loading and elution of antibiotics commonly used to prevent and treat bone infections. Specifically, in the new scaffold formulations we will use two polymers that have different abilities to uptake and release water, allowing us to control the rate at which antibiotics are loaded and released from the scaffolds. We expect that these next-generation NuCress™ scaffolds will have an enhanced ability to deliver large amounts of antibiotics. We will test the ability of the redesigned scaffolds to release antibiotics on the laboratory bench and in a small animal model of bone infection (rabbits). The scaffolds that perform best in rabbits in preventing infection and healing bone gaps will be tested in a large animal model of bone injury. By the end of the proposed project, we will have sufficient data on the antibiotic-optimized NuCress™ scaffold to submit it for premarket approval.

Fiscal Year 2018 Joint Warfighter Medical Research Program Focus Area

Military Benefits: Our scaffold could shift the bone gap treatment paradigm, introducing a dual regenerative and infection-mitigating device at the first battlefield surgical element. All explosion wounds are complicated by dirt, bomb fragments, clothing fibers, and other foreign matter. This contamination causes infection in a fourth of all severe tibial fractures resulting from combat in US and UK soldiers, delaying and complicating healing and increasing the risk of morbidity. The NuCress™ scaffold’s proposed use as an antibiotic delivery system would directly address the need for early, fast infection fighting, delivering drugs directly to the wound site and not requiring future surgeries for removal, as many infection- fighting devices do. The ability to simultaneously regenerate bone and deliver clinically relevant drug concentrations represents a transformative improvement to current medical technology.

The NuCress™ scaffold is designed to be used by medics at far forward operating locations. The scaffold we propose could be integrated into existing wound cleaning and treatment protocols and be inserted immediately after the wound has been cleaned by the medic at Roles II and up. The scaffold does not require special tools to use and stays in the bone gap without glue or screws. The medic must simply cut the scaffold to fit the size of the bone gap, load the scaffold with their antibiotic of choice, and apply to the bone gap. The scaffold will deliver antibiotics to prevent bacterial infection and facilitate bone repair. If bone repair required additional surgeries at a later date, e.g., after patient stabilization and evacuation from the field hospital, the inexpensive antibiotic-impregnated scaffold could be easily removed, if needed, and replaced with a second implant (either a standard NuCress™ scaffold, an antibiotic-impregnated scaffold, or a scaffold loaded with growth factors). This simple, easy-to-use, PFC-specific solution to prevent infection and prepare bone injuries for future advanced treatment would fundamentally change the outlook for bone injuries sustained in austere environments.